Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States.
Org Lett. 2023 Feb 17;25(6):956-960. doi: 10.1021/acs.orglett.2c04287. Epub 2023 Feb 2.
The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyrate. The novel -sulfinyl silylenamine reagent enabled the key step, with three-component domino Michael/Michael/Mannich annulation providing the 1-amino-2,4-diester scaffold with four new chiral centers, and access to the isoquinuclidine in high yield (84%) and diastereoselectivity (>95:5 dr).
伊博格碱类化合物是很有前途的抗成瘾和神经再生候选药物，可用于医学治疗。由于合成困难，C20-表伊博格碱类化合物的研究较少。在此，我们报告了从三甲基原丁酸酯经 7 步反应以最短的路线合成 (+)-表伊波加明，其中关键步骤采用了新型 -亚磺酰基硅亚胺试剂，通过三组分多米诺迈克尔/迈克尔/曼尼希环加成反应，以高收率（84%）和高非对映选择性（>95:5 dr）构建了 1-氨基-2,4-二酯骨架和异喹啉啶，提供了四个新的手性中心。
